The proposed research investigates the ability to respond flexibly and appropriately when a situation affords multiple possible responses. This aspect of executive function is compromised in many disorders affecting prefrontal cortex (PFC), contributing to problems in communication, planning, and decision-making. The research aims, first, to identify neural substrates supporting this flexibility, and second, to explore potential neural mechanisms. Progress in adjudicating between competing theories of the role of PFC regions in flexible responding has been limited by flawed measures and failure to manipulate demands within the same task. Two fMRI studies remedy these problems, in order to cleanly differentiate regions supporting controlled retrieval of responses, selection between competing task-relevant responses (underdetermined competition), and selection of a task-relevant response in the face of prepotent task-irrelevant competitors. There is debate as to the role of ventrolateral PFC (VLPFC) in selection versus controlled retrieval. The first study uses new unconfounded measures to identify VLPFC regions supporting these processes. Selection in the face of prepotent competition has been found to tap regions of dorsolateral PFC (DLPFC) as well as VLPFC, but has not been contrasted with selection when there is underdetermined competition. A second study will contrast these two forms of competition. The second aim is to bridge levels of analysis, probing the mechanisms supporting controlled retrieval and selection using a neural network model. The model will allow investigation of the effects of NMDA receptor, GABA, and dopamine function which may contribute to cognitive control deficits in conditions such as schizophrenia, anxiety disorders and ADHD. A better understanding of the neural substrates and mechanisms supporting executive function is critical for developing better behavioral and pharmacological interventions to treat such cognitive control deficits. Relevance: We are constantly faced with the task of choosing one option from among many, such as when we select words to express a thought. This ability is impaired in many disorders, including ADHD, anxiety, and schizophrenia. These studies explore how the brain is able to choose between multiple options, and how these disorders may affect this ability, with the goal of aiding development of new treatments.